Insulin receptors appear upon the membrane of lymphocytes activated by mitogens, skin and renal allografts, GVH, MLC, chronic infections, and tumors as shown in the proposed studies. As the receptor emerges, the hormone insulin becomes capable of modulating the intracellular levels of cyclic nucleotides, cAMP ad cGMP thus supporting facilitated transport of amino acids and glucose and providing an amplification signal for cytotoxic lymphocyte destruction of target. The pharmacokinetic principles, chemical nature, temporal relationships that govern the emergence of this insulin receptor will be studied and applied to early and more accurate tissue typing of cadaveric human transplantation, to the assessment of allograft immunity once the graft has been placed, and to immune function in diabetes mellitus. These studies seek to interdigitate an understanding of the chemistry and pharmacology of the cellular control of immune response with clinical strategies applied to transplantation and diabetes mellitus.